In the last quarter century, the use of brain imaging for the treatment and understanding of diseases and genetic flaws has grown dramatically following the introduction of Computerized Tomographic X-Ray (CT) in 1972 followed in 1982 by magnetic resonance imaging (MRI). The reason for this growth and importance in brain imaging is that neurologists, psychiatrists and neuroscientists utilize and attach substantial importance to high resolution, three-dimensional, anatomical images of the brain. The development of functional brain imaging which seeks to map the distribution of brain activity has closely followed the development of structural imaging which maps some physical property of the brain such as tissue density.
While SPECT is playing an important role in functional brain imaging, it has been limited in many applications by its low spatial resolution. The tiny structures of the brain where thinking and other neuronal activity takes place are much smaller than the resolution of the best SPECT scanners and, therefore, are not seen. This situation is even further complicated where brain imaging is performed on a small animal such as a rat or mouse. The brain structures of such animals are much smaller than a human brain structure and, therefore, the resolution of conventional SPECT scanners is grossly inadequate.
In general, the typical clinical resolution of the best SPECT rotating gamma-cameras as well as PET and functional MRI, is about 9, 7 and 3 mm, respectively. One area of improvement used to bring rotating gamma-cameras to their state-of-the-art is modifying the original parallel hole collimator design to the higher performance mildly converging tapered hole designs while increasing camera size in order to maintain a sufficiently large field-of-view.
In recent years, small animal imaging has been the subject of intense research and development. This is largely due to the advances in molecular and cell biology, the use of transgenic mice models and the availability of new imaging tracers. The genetic similarity of mice to humans has enabled a wide range of human diseases to be studied in animal models. The completion of the sequence of the human genome will improve our understanding of human biology at the molecular level and create new and improved models of human diseases. Transgenic mice have been widely used in the study of cancer mechanisms and from modeling human diseases.
Recently, the study of transgenic mice has opened new prospects in evaluating human gene therapy by non-invasive, repetitive and quantitative imaging of gene expression. It is of interest in drug discovery and development to map the concentration of experimental, bioactive molecules in the body of a mouse or other laboratory animal. This is typically done by tagging the molecules with a gamma-ray emitting atom (radioisotope) and then externally scanning the animal with directionally sensitive gamma ray detectors. This modality, as discussed above, is called “SPECT” (Single Photon Emission Computed Tomography).
For example, animals injected with molecules tagged with radioisotopes, for example, a neurotransmitter such as dopomine, may be tagged with, among others, low energy photon emitting I-125 which may be desirable because it has a half-life of almost 60 days, is readily available and also has sufficient energy of the low energy photon to escape from the tissue of the animal.
The emitted gamma rays are generally collected by devices known as collimators. Collimators are traditionally blocks of lead with holes drilled or cast in them. The holes permit gamma rays, which are traveling in a specific direction, to pass through the holes in the blocks or, in other words, the holes in the collimator specify the flight direction of gamma rays received from a single photon emission radio-nuclide. Any gamma rays not passing through the hole(s) are blocked, i.e., absorbed, by the lead structure of the collimator. The longer or narrower the holes, the more precise or specific the direction, i.e., the flight path of the gamma ray can be determined. This is good for geometrical, spatial resolution, i.e., better for determining where the emitted gamma ray came from, but bad for sensitivity. It is bad for sensitivity because the longer and narrower the hole(s) the fewer gamma rays will pass through the hole to impact on the scintillation crystal.
The basic structure of the collimator is thus a hole with a finite length and aperture size. The photons, which pass through an individual hole, are not only photons entering a hole parallel to the hole axis, but also photons entering the hole at a small angle to the hole axis. As a result, each hole accepts all of the photons in a cone at a small vertex angle. This is the reason why the spatial resolution of the collimator is a function of the distance between a source emitting the photons and the collimator surface.
It is known in the field to fabricate a focusing collimator as a thick block or sheet of gamma-ray absorbing material (such as lead) that has a plurality of holes through it. All holes point to the same place in space, the focal point, in front of the collimator. Thus, in the thick sheet the holes must be angled relative to a central axis of the collimator, in order to be aimed at the focal point. In the Applicant's full size human brain SPECT scanner, the collimator is made of lead that is 4 inches thick. The focal point lies 6 Inches in front of the collimator. In other words, if you place your eye at the focal point and look towards the collimator, you will see through all holes at once. A gamma-ray sensitive crystal, also known as a scintillator, is placed behind the collimator and will register far more gamma rays, i.e., obtain more counts, when the source is located at the focal point than if it is located anywhere else.
Focusing collimators having tapered holes are vastly superior than straight, parallel holes as typically used in gamma cameras in that they provide both better geometrical resolution and sensitivity at the same time. However, manufacturing a collimator small enough for adequate precision in both geometrical resolution and sensitivity for small animals is very difficult, inefficient and expensive using machined or cast lead blocks.
The collimator, whether in a reduced size for small animals or sized for use with a human, is merely one part of the entire scanning machine. In either machine, the collimators are arranged in a substantially circular fashion about a longitudinal axis of a source, either human or animal, to obtain a 3-D convolution of the brain. The brain scanner mechanically moves the focusing collimators, i.e., the focal points of the focusing collimators, in such a way that they uniformly sample a single transaxial plane of the human or animal, i.e., a transaxial slice normal to a longitudinal head to toe axis of the human, at one time. In order to do this, the collimators are moved by a supporting gantry in such a way that they simultaneously translate across the slice in one direction. When a line is completed, the collimators increment out (or in) and then translate across the slice in the opposite direction.
The process is repeated until a raster scan of the slice is completed by all collimators. The brain scanner scans a transaxial slice 200 mm in diameter (field of view) and produces images with a resolution of about 2.5 mm. This is known as scanning focal point technology and it is unique in nuclear medicine. The total volume of the brain is sampled by incrementally stepping the bed carrying the human patient or animal axially at the completion of each slice. A more detailed description of the collimator travel and scan movement is discussed and known from Stoddart, U.S. Pat. No. 4,209,700 and, therefore, a further detailed discussion of the same is hereby incorporated by reference.